| Co-Investigator(Kenkyū-buntansha) |
ITOH Souichiro Tokyo Medical and Dental University, 疾患遺伝子実験センター, Associate Professor (10242190)
SHINOMIYA Kenichi Tokyo Medical and Dental University, 大学院・医歯学総合研究科, Professor (20111594)
TAKEDA Shu Tokyo Medical and Dental University, 大学院・医歯学総合研究科, Lecturer (30376727)
小山 富久 生体材料工学研究所, 助手 (70361714)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2005: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Research Abstract |
We have developed continuous weight bearing disc degeneration model for mouse tail. In this model, degradation of IVD was observed within two weeks after operation. Using this model, we tested if weight loading, a most common cause of intervertebral disc (IVD) degeneration, induces Runx2 expression, which may cause chondrocyte hypertrophy. Indeed, weight loading of the IVD by compression for a day significantly increased Runx2 expression. Thus, we next examined the expression of Runx2 with other disc degradation markers in canine IVD, The expression of RUNX2, type-X collagen and MMP-13 mRNA in young intact and degenerated IVD were examined by semi-quantitative RT-PCR analysis. The localization of Runx2 and type-X collagen protein in control and degenerated IVD were examined by imunohistochemistly. The expression of RUNX2 transcript and protein, in combination with type-X collagen and MMP-13, was enhanced in degenerated IVDs of the dog. RUNX2 co-localizes with MMP-13 in clusters of chondrocytes in fibrillated OA cartilage, and MMP-13 expression is regulated by Runx2 in osteoarthritis chondrocytes. Type-X collagen and MMP13 are downstream targets of Runx2 in the growth plate chondrocytes. Considering IVD cells all express cartilage-specific matrix proteins with quantitative differences, depending on their anatomic situation, the comparable molecular regulation may exist in IVD cells, articular chondrocytes and growth plate chondrocytes.
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